In recent years, numerous drugs have been proposed for aiding the return to normal concentrations of the various lipid components of the serum, in consideration of the particular seriousness of hyperlipidemias and dislipidemias in the etiopathogenesis of numerious illnesses, including illnesses of social interest. These drugs can be distinguished schematically in the following manner by their action mechanism:
(1) those which inhibit the intestinal absorption of cholesterol; PA1 (2) those which act on the secretion of bile acids; PA1 (3) those which inhibit the synthesis of cholesterol and the mobility of the fatty acids of the adipose tissue; PA1 (4) those which activate fibronolysis and thrombolysis; and PA1 (5) those which favor increase in the removal of lipoproteins. PA1 (a) On hydrolysis FAPA liberates hexosamine, uronic acids and sulphates in the molar ratios of approximately 1/1/1 with variable quantities of nucleosides. PA1 (b) Electrophoretically, FAPA separates into three anionic bands distinguishable with Alcian Blau and Toluidine Blue. PA1 (c) FAPA reacts with alkaline and alkaline earth metals to form salts which are very soluble in water, whereas the salts which it forms with the aliphatic ammonium ion are insoluble. PA1 (d) The sodium salt is 2% soluble in 50% ethyl alcohol, whereas, the acid form is 2% soluble in 70% ethyl alcohol. PA1 (e) FAPA reacts with Toluidine Blue to give a minimum metachromatic reaction (approximately 1/10 of that given by heparin). PA1 (f) Spectrophotometrically, it shows a maximum of 260.+-.1 nm. PA1 (g) FAPA shows a rotatory power on polarised light of -11.degree. to -22.degree.. PA1 (h) The infrared spectrum of the substance determined in KBr, to which the graph of FIG. 1 refers, shows the following functions: EQU --COOH EQU --NHR EQU --COCH.sub.3 EQU --OSO.sub.3 H EQU --CH.sub.2 OH PA1 From the total analytical data it can be established that FAPA has the following structure: ##STR1## wherein R.sub.1 and R.sub.2 are --H or SO.sub.3 H, R.sub.3 is --SO.sub.3 H or --CO--CH.sub.3, and m, n, p are whole numbers which can vary over a wide range and define a molecular weight of 10,000 to 30,000 daltons for the polysaccharide chains. PA1 (1) removing and immediately grinding the aortas of young mammals which have just been slaughtered; PA1 (2) homogenising and suspending said tissues in water or suitable saline solutions; PA1 (3) attack by proteolytic enzymes such as trypsin, chymotrypsin, pancreatin, papain, ficin or bromelin, under the respective optimum pH, temperature and time conditions; PA1 (4) separating the digested liquid by filtration and collecting same; PA1 (5) precipitating FAPA from the digested liquid by solvents miscible with water and/or by forming insoluble salts with the aliphatic ammonium ion; and PA1 (6) purifying by salification with alkaline or alkaline earth metal bases, decolouration with permanganate, treatment with alkali at 70.degree. C. for eliminating the terminal parts of the residual peptide chains, separation of the desired salt form with solvents (sodium, potassium, calcium salts, etc.), filtration, sterilization and lyophilisation. PA1 (1) Action of experimental arteriosclerosis PA1 (2) Biological activity PA1 (3) Product Tolerance PA1 (a) Toxicity: FAPA proved to be well tolerated by rats, rabbits and guinea pigs treated either by parenteral administration or by oral administration with per diem doses of 200 mg/kg.
Among these latter drugs, heparin and analogous substances generally known as heparinoids have assumed special importance in the treatment of hyperlipidemias and dislipidemias.
Among the various pharmacological actions of heparin, one of particular importance is the so-called clarifying action which consists essentially of inducing the appearance in the bloodstream of lipoproteinlipase, a physiological enzyme which separates the ester bonds of triglycerides to transform them into monoglycerides and free fatty acids. This action is entirely independent of the anticoagulating action, which represents the negative side and determines the limit of use of heparin in this type of therapy.
Again, within the field of antiarteriosclerotic therapy, it has been stated in published works (Comi and Coll., Boll, Chim. Farm. 106/5/309/21 (1967); French Pat. No. M 4,871filed Nov. 24, 1965) that by administering total aorta extracts to rabbits which have been made hypercholesterolemic by means of chloresterol-base diets, a strong reduction in atheromatosis formations have been obtained. On the other hand, it has been shown (Dall'Occhi and Coll. Adv. Exi. Med. Biol. 1967 1,468/83) that the total aorta extract leads to reactions of immunity with harmful effects on the pulmonary arteries.